1. Field of the Invention
A pharmaceutical nasal spray formulation of ketorolac tromethamine for the treatment of pain such as caused by postoperative pain, cancer pain and migraine headache. When administered intranasally to a mammal, the necessary blood level of the drug is provided to effectively treat the pain.
2. Description of Related Art
The intranasal route of administration provides an effective and convenient means of drug delivery, especially when the most popular route, the oral route, is inappropriate and/or ineffective. The nasal route offers some advantages such as by-passing the metabolic limitation pathways of gastrointestinal tract and liver, thereby significantly increasing the effectiveness of the drug. The nasal mucosa offers a large surface area and relatively low enzymatic degradation resulting in a rapid absorption of drugs into the systemic circulation producing high plasma levels similar to those provided by injections. While parenteral administration also bypasses the gastrointestinal tract and delivers the drug formulations directly into the bloodstream and the surrounding tissues of the recipient, it has several disadvantages such as pain of injection, inconvenience and thus poor patient compliance. In past several years, the effectiveness of this route for delivery of certain drugs such as insulin, calcitonin and testosterone has been documented, Dondeti, P.; Zia, H.; and Needham, In Vivo Evaluation of Spray Formulations of Human Insulin for Nasal Delivery, Int. J. Pharm. 122, 91 (1995); Dondeti, P.; Zia, H.; and Needham, E. E., Bioadhesive and Formulation Parameters Affecting Nasal Absorption, Int. J. Pharm., 127, 115 (1996); Dua, R.; Zia, H.; and Needham, T. E., The Influence of Tonicity and Viscosity on the Intranasal Absorption of Salmon Calcitonin in Rabbits, Int. J. Pharm., 147, 233 (1997); and Ko, K. T.; Zia, H.; Needham, T. E.; Testosterone Emulsion Formulations of Nasal Administration, J. of Microencapsulation, Accepted Nov. 10, 1996.
Ketorolac tromethamine is a highly potent non-narcotic analgesic with a moderate anti-inflammatory activity. It is efficacious in treating pain arising from a broad spectrum of causes, such as postoperative pain, cancer pain, migraine headache and pain from dental extractions, Suayib, Y.; Ibrahim, G.; Gulten, T.; Cermil, S.; Ketorolac Tromethamine in Cancer Pain, Acta Oncologica 36 231-232, (1997); and DeAndrade, R. J.; Maslanka, M.; The Use of Ketrolac in the Management of Postoperative Pain, Orthopedics, 17, 157-166, (1994). Several recent studies have examined the use of ketorolac in the emergency treatment of migraine headache via injections. An intramuscular injection of 60 mg dose of ketorolac was found to be as effective as meperidine and hydroxyzine in treating migraine headaches. It provided a significant reduction of symptoms in approximately 30 minutes to 1 hour after intramuscular administration and lasted for 6 hours. The emergency management of migraine headache is based on rest and the administration of antiemetics and analgesics. The use of dihydroergotamine (DHE) in the emergency department is limited because of its side effects including vomiting. The problems facing the emergency physicians when treating migraine, include narcotic abuse and the liability of releasing patients who had received central nervous depressants. Ketorolac has less adverse side effects than narcotic drugs, does not have the side effects associated with DHE and has not been shown to have physiological addictive potential, this drug appears to be an excellent choice for treating migraine headache.